The long-term goals of this project are the discovery and development of new, selective synthetic reactions which can be applied in more efficient syntheses of complex anti-tumor natural products and analogs. In some cases, these new reactions constitute simple models of the enzymic processes which operate in biosynthetic pathways. The specific aims of this proposal concern substituent-directed oxidation reactions in which the attach of a metal oxide on an organic substrate such as an alkene is mediated by prior coordination of the oxidant with a ligand group present in the substrate, as is shown schematically below left. This methodology should result in greater selectivity and product control for allylic oxidations and oxidative cyclizations. This proposal contains two parts. The first part of the proposal describes a study of the mechanism and scope of these reactions. A series of model compounds will be prepared and subjected to various reaction conditions, and the composition of the products and the rate of reaction will be monitored by appropriate spectroscopic techniques. Correlations will be established between the selectivity observed, and the reaction conditions and substrate structure, with the goal of establishing a predictive rationale. The second part describes an approach to the total synthesis of the anti-tumor agent Chapliatrin using the new methodology in a key oxidative cyclization step.